HTS assay for modulators of expression of RBM3 in drug-resistant prostate cancer

Grant Winners

Dean

Abstract

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths in men in the US [1]. There are multiple drugs including hormonal therapies used to treat PCa, however, resistance, and subsequently, metastasis often occur. Although some treatments have efficacy, there are currently no cures for metastatic PCa, which necessitates novel approaches to address this problem. Our preliminary data show that over-expression of RNA-binding Motif 3 protein (RBM3) decreases aggressiveness and stem cell likeness of PC3 prostate cancer cells. Based on these data, we hypothesize that small molecules capable of upregulating stress-response protein RBM3 in the taxane-resistant PCa cells will help to address lack of therapies for metastatic PCa. To test this hypothesis we propose to (1) develop taxane-sensitive and taxane-resistant stable cell lines expressing RBM3-GFP using PC3 lines; (2) develop high throughput screening (HTS) assays, and (3) perform a screen, identify and characterize compounds that modulate expression of RBM3. These studies will serve as a proof-of-principle that pharmacologic modulation of RBM3 expression levels can be used as a therapeutic approach to resistant prostate cancer.

Our expected outcome is the ability to use novel compounds as probes of RBM3 to deepen our understanding of prostate cancer with a longer-term outcome to develop novel therapeutic options for the disease. Our team is uniquely positioned to achieve these goals due to expertise in prostate cancer (Getzenberg) and drug/probe discovery (Minond).